Proposed Meropenem Breakpoints for Interpretation of Antimicrobial Susceptibility Testing of Bacteria Isolated From Dogs

Abstract

Meropenem is a carbapenem antibiotic used infrequently in veterinary medicine. However, antimicrobial susceptibility testing standards are needed to monitor for resistance caused by carbapenem resistant Enterobacterales (CRE). The Clinical and Laboratory Standards Institute (CLSI) does not have veterinary-specific carbapenem breakpoints for testing bacteria isolated from animals. Our objective was to correct this deficiency and propose clinical antimicrobial susceptibility testing breakpoints for consideration by clinical laboratories, standard-setting organizations, and for monitoring and surveillance programs. We collected pharmacokinetic data from published studies, which were entered into a forecasting program to perform 10,000 Monte Carlo Simulation using a range of dosages considered for administration of meropenem to dogs. Our target for the simulations was a 90% Probability of Target Attainment (PTA) to reach a time-above-MIC for the unbound fraction of the drug (f T > MIC) for at least 40% of the dosing interval. Our results showed that this target can be met for a MIC of ≤ 1 μg/mL (Enterobacterales) with a dose of 20–30 mg/kg IV every 8 h or 10 mg/kg every 6 h. For a one-step higher dilution of ≤ 2 μg/mL (Pseudomonas aeruginosa), a dose of 20–30 mg/kg every 6 h is needed. Therefore, we propose new clinical MIC breakpoints for antimicrobial susceptibility testing these bacteria isolated from dogs of ≤ 1, 2, and ≥ 4 μg/mL for the Susceptible, Intermediate, and Resistant category, respectively, for testing bacteria of the Enterobacterales, and values of ≤ 2, 4, and ≥ 8 μg/mL, respectively, for testing P. aeruginosa.